Department of Medicine I and Cancer Center, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.
Military Medical Institute, Warsaw, Poland; San Camillo and Forlanini Hospitals, Rome, Italy; Eli Lilly and Company, Indianapolis, IN; i3 Statprobe, Ann Arbor, MI; Gustave Roussy Cancer Institute, Villejuif, France.
To assess antiangiogenic effects of enzastaurin in combination with sunitinib in patients with renal cell carcinoma (RCC).
This was a multicenter, phase 2 study of enzastaurin and sunitinib versus placebo and sunitinib for adult patients with metastatic clear cell RCC. Part 1 was a 6-week, open-label, safety lead-in phase with 2 cohorts (sunitinib, both cohorts: 50 mg/d for 4 weeks; enzastaurin, cohort 1: a loading dose of 500 mg, followed by 250 mg daily; cohort 2: a loading dose of 1125 mg, followed by 500 mg daily). Part 2 was to be a randomized, double-blinded phase, with efficacy as the primary objective. Secondary objectives included the assessment of treatment-emergent adverse events (TEAEs) and pharmacokinetics.
Seventeen patients received ≥1 dose of study medication. Six patients (54.5%) in cohort 1 and 2 patients (33.3%) in cohort 2 received ≥6 cycles of treatment. All patients experienced ≥1 TEAE possibly related to study drug. Dose reductions were required as follows: cohort 1-enzastaurin, n=4 (36.4%), sunitinib, n=6 (54.5%); cohort 2-enzastaurin, n=3 (50.0%), sunitinib, n=2 (33.3%).
Whereas the hypothesis that combining sunitinib and enzastaurin may result in greater antiangiogenic effects in RCC is based on solid scientific evidence, part 2 of the study was not activated due to the high number of TEAE-related dose reductions at the expected efficacious dose and overall decision by the sponsor not to pursue further development of enzastaurin for solid tumors.
Written by:
Schmidinger M, Szczylik C, Sternberg CN, Kania M, Kelly CS, Decker R, Hamid O, Faelker T, Escudier B. Are you the author?
Reference: Am J Clin Oncol. 2011 Jun 4. Epub ahead of print.
PubMed Abstract
PMID: 21654314
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